The present invention relates to an adsorbent for bradykinin, a process for adsorbing and removing the same using the adsorbent, and an adsorber of the same.
Bradykinin is a physiologically active peptide consisting of nine amino acids, which was discovered by Rochae Silva in 1949. It is known that bradykinin has various activities, such as a hypotensive effect and an increase in vascular permeability via vasodilation, a contractive effect on smooth muscle, and the like.
The mechanism for production of bradykinin is considered to be as follows. First, blood coagulation factor XII is activated into blood coagulation factor XIIa by insoluble materials such as glass, kaolin or the like having negative charge on their solid phase surface, eladic acid, trypsin, plasmin or kallikrein. The blood coagulation factor XIIa then converts prekallikrein in blood into kallikrein. The kallikrein in turn reacts with high molecular weight kininogen in blood to release bradykinin. On the other hand, the kallikrein produced during this process has a property of activating blood coagulation factor XII (positive feedback). The released bradykinin is degraded by kininase II (which is the same enzyme as the angiotensin I converting enzyme).
Recently, hemocatharsis by means of an extracorporeal circulation has been extensively carried out. It has become a problem that, upon the hemocatharsis, bradykinin sometime happens to be produced due to a contact of some kind of medical materials with blood and/or plasma to cause a shock-like symptom. In the case of septicemia, it is consdered that bradykinin is produce due to an endotoxin to cause hypotension which induces shock.
The mechanism of the production of bradykinin due to some kind of medical materials is hypothesized as follows. Prekallikrein exists in blood which is bound to high molecular weight kininogen. Some kind of medical materials have a property of adsorbing both of the prekallikrein/high molecular weight kininogen complex and the blood coagulation factor XII. Thus, substances involved in the production system of bradykinin are gathered which promote the production of bradykinin.
Under these circumstances, development of an adsorbent for removing bradykinin from blood has been desired. As an adsorbent for removing bradykinin from blood, an adsorbent with a hydrophobic property is disclosed in Japanese Laid-Open Publication No. 6-296861 and No. 6-296864 in the name of ASAHI MEDICAL CO., LTD.. However, since, in general, hydrophobic materials adsorb critical proteins in blood as well, these materials are inappropriate as materials for hemocatharsis.
As a result of the extensive investigation on an appropriate carrier to remove the above-mentioned bradykinin, the inventors found that a styrene-divinylbenzene copolymer having sulf onic acid groups was effective for such a removal. Based on this finding, the inventors obtained the present invention.
The present invention provides an adsorbent for bradykinin comprising a styrene-divinylbenzene copolymer having sulfonic acid groups.
In one embodiment, an ion exchange capacity of the styrene-divinylbenzene copolymer having sulfonic acid groups is between about 0.01 meq/ml and about 5 meq/ml.
The present invention also provides a method for removing bradykinin, wherein the method comprises contacting an adsorbent comprising a styrene-divinylbenzene copolymer having sulfonic acid groups with a fluid containing bradykinin.
In one embodiment, an ion exchange capacity of the styrene-divinylbenzene copolymer having sulfonic acid groups is between about 0.01 meq/ml and about 5 meq/ml.
In one embodiment, the adsorbent is charged in a vessel having an inlet and an outlet for a fluid.
In one embodiment, the vessel is incorporated in an extracorporeal circulation circuit.
The present invention further provides an adsorber for adsorbing bradykinin, wherein the adsorber comprises a vessel which has an inlet and an outlet for a fluid and the vessel is charged with an adsorbent for bradykinin comprising a styrene-divinylbenzene copolymer having sulfonic acid groups.
In one embodiment, the adsorber is equipped with a means for preventing the adsorbent from flowing out of the vessel.
The present invention further provides a method for treating a disease of which the causal agent is bradykinin, wherein the method comprises contacting an adsorbent comprising a styrene-divinylbenzene copolymer having sulfonic acid groups with a body fluid from a patient with the disease.
In one embodiment, the adsorbent is charged in a vessel having an inlet and an outlet for a fluid.
In one embodiment, the vessel is incorporated in an extracorporeal circulation circuit.
In one embodiment, the disease is an inflammatory disease.